INS and metabolic syndrome: It has been reported that in DIO mice, increasing cGMP via sGC stimulation or phosphodiesterase (PDE5)-inhibition increases insulin sensitivity, thus alleviating some of the consequences of metabolic syndrome (Hoffmann et al., 2015); however, in these previous studies, because body weight gain was lower in compound-treated animals, the metabolic benefit could not be fully attributed to sGC stimulation or PDE inhibition.